Role of microRNAs in the main molecular pathways of hepatocellular carcinoma

Vasuri, Francesco; Visani, Michela; Acquaviva, Giorgia; Brand, Thomas; Fiorentino, Michelangelo; Pession, Annalisa; Tallini, Giovanni; d’Errico, Angelo; Biase, Dario de

doi:10.3748/wjg.v24.i25.2647

Cited by 78 publications

(62 citation statements)

References 121 publications

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“…In this manner, miRNAs have been demonstrated to serve crucial roles in a wide range of physiological processes including cell proliferation, cell cycle progression, differentiation, metabolism, metastasis and tumorigenesis (14). In particular, accumulating evidence supports that miRNAs are aberrantly expressed in a substantial number of human disorders including cancer (15)(16)(17); with changes in miRNA expression being reported in HCC (18), colorectal cancer (19), lung cancer and bladder cancer (20,21). In HCC alone, miRNAs have been implicated either as oncogenes or tumor suppressors during oncogenesis and development (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein�1

et al. 2019

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Emerging studies have revealed that microRNAs (miRNAs) are aberrantly expressed in hepatocellular carcinoma (HCC), and the dysregulation of miRNAs exerts crucial roles in the carcinogenesis and development of HCC. Therefore, elucidating the relationship between miRNAs and HCC progression is of great importance to develop novel therapeutic techniques and to improve the prognosis of patients with this malignancy. Recently, miR-548b-3p (miR-548b) has been demonstrated to be a cancer-associated miRNA in tongue squamous cell carcinoma and glioma. However, the expression and function of miR-548b in HCC remain poorly understood. In the present study, it was found that miR-548b is expressed at low levels in HCC tissues and cell lines. Decreased miR-548b expression was found to be positively associated with the clinical features of HCC, including the TNM stage and lymph node metastasis. Functional experiments revealed that upregulation of miR-548b expression decreased proliferation and invasion of HCC cells. Specificity protein 1 (SP1) was verified to be a direct target of miR-548b in HCC cells; as Spearman's correlation analysis identified miR-548b expression to be negatively correlated with that of SP1 expression in HCC tissue specimens. In addition, SP1 inhibition exhibited similar effects as miR-548b overexpression in HCC cells. SP1 reintroduction significantly reversed the suppressive effects of miR-548b upregulation on the proliferation and invasion of HCC cells. In conclusion, the results presented in the present study demonstrated that miR-548b may serve as a tumor suppressive miRNA that inhibits the proliferation and invasion of HCC cells by directly targeting SP1. Consequently, miR-548b can be exploited as a novel therapeutic target for treating patients with HCC in the future, but this needs to be investigated further.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein�1

et al. 2019

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“…The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been regarded as one of the main molecular pathways in HCC progression 12 . STAT proteins, including STAT1-6, exhibit promoting or suppressive effect on antiviral response, inflammation, and tumorigenesis in liver, one of which, STAT5, could promote liver damage 13 .…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2

Ren

et al. 2019

Cell Death Dis

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microRNAs (miRNAs) play essential roles in progression of hepatocellular carcinoma (HCC). However, the roles of miR-196a and miR-196b as well as mechanism in HCC progression remain poorly understood. The expressions of miR-196a, miR-196b and suppressor of cytokine signaling 2 (SOCS2) were measured in HCC tissues and cells by quantitative realtime polymerase chain reaction or immunohistochemistry. HCC progression was investigated by cell proliferation, glycolysis, cycle, clones, apoptosis, and necrosis. The interaction between SOCS2 and miR-196a or miR-196b was explored by luciferase activity and RNA immunoprecipitation analyses. The expressions of proteins in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway were measured by western blot. A xenograft model was established to investigate the roles of miR-196a or miR-196b in vivo. We found that miR-196a and miR-196b were highly expressed in HCC tissues and cells. High expression of miR-196a or miR-196b was correlated with tumor size, tumor-node-metastasis stage, lymph node metastasis, albumin-bilirubin grade and poor 5-year survival. Knockdown of miR-196a or miR-196b suppressed cell proliferation, glycolysis, cell cycle process, colony formation but induced apoptosis or necrosis in HCC cells. SOCS2 was targeted by miR-196a and miR-196b and its interference ablated abrogation of miR-196a or miR-196b-mediated inhibitory effect on HCC progression. SOCS2 was negatively associated with activation of the JAK/STAT pathway. Besides, knockdown of miR-196a or miR-196b limited xenograft tumor growth by blocking the JAK/STAT pathway. We concluded that downregulation of miR-196a or miR-196b inhibited HCC progression through regulating the JAK/STAT pathway via targeting SOCS2, providing novel targets for prognosis and therapeutics of HCC.

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“…A growing body of articles has explored numerous molecules year on year, hoping to clear the underlying molecular mechanisms of HCC and contribute to its diagnosis and treatment. Some of them have manifested vital roles in HCC carcinogenesis, such as metadherin [22][23][24]. However, so far, there has been no valid target protein-especially a protein located in the Golgi complex which could be the target for HCC diagnosis and treatment, making it necessary to be explored.…”

Section: Discussionmentioning

confidence: 99%

Clinical Value and Potential Mechanisms Exploration of GOLGA8B in Hepatocellular Carcinoma: A Comprehensive Investigation Based on Real-Time Quantitative Polymerase Chain Reaction, RNA-seq, Microarray and Immunohistochemistry

Ma¹,

Zhai²,

Wu³

et al. 2019

Preprint

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Introduction Recent studies found that GOLGA8B plays an essential role in different cancers. However, the role GOLGA8B plays in the carcinogenesis and development of hepatocellular carcinoma (HCC) remains unclear. This study explores the clinical significance and prospective mechanisms of GOLGA8B in HCC. Materials and methods The expression of GOLGA8B was detected in tissues of HCC and non-HCC controls. A real-time quantitative polymerase chain reaction analysis was performed to evaluate the mRNA expression of GOLGA8B. RNA-sequencing data and microarray chip data were obtained for further analysis. The role GOLGA8B plays in patients with HCC was also evaluated. An immunohistochemistry (IHC) analysis was also performed to evaluate the protein expression of GOLGA8B. The different GOLGA8B expression resources, including mRNA and protein expression, were integrated by calculating standard mean difference (SMD) and summary of the receiver operator characteristic (sROC). Genes co-expressed GOLGA8B were predicted. Enrichment analyses including Gene ontology (GO) and biological pathway were performed to investigate the essential molecular mechanisms. Hub genes were screened out by a protein-protein interactions network. MicroRNAs which target GOLGA8B at a posttranscriptional level were also predicted. Results According to different resources, GOLGA8B manifested a higher expression in tissues of HCC than in non-HCC controls and exhibited clinical values for HCC. The RT-qPCR analysis revealed an increasing trend of GOLGA8B expression in HCC. GOLGA8B expresssion was significantly increased in RNA-sequencing and 7 of 13 microarray chip. IHC analysis also revealed significantly higher expression of GOLGA8B protein. Moreover, GOLGA8B expression was correlated with pathologic tumors and stages according to RNA-sequencing data and IHC analysis. The integrated SMD and sROC of different resources was 0.893 (P=0.004) and 0.79. A total 1303 co-expressed genes were gathered to perform enrichment analyses. The most significant biological pathways of co-expressed genes were spliceosome and mitogen-activated protein kinase signalling (MAPK). Four hub genes (SF3B1, HNRNPA2B1, HNRNPA1 and SRRM2) and five miRNAs (miR-369-3p, miR-203a, miR-374b-5p, miR-139-5p and miR-144-3p) were screened out. Conclusion GOLGA8B expression was increased in HCC and may serve as a novel target for HCC diagnosis and treatment.

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Role of microRNAs in the main molecular pathways of hepatocellular carcinoma

Cited by 78 publications

References 121 publications

MicroRNA‑548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein�1

MicroRNA‑548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein�1

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2

Clinical Value and Potential Mechanisms Exploration of GOLGA8B in Hepatocellular Carcinoma: A Comprehensive Investigation Based on Real-Time Quantitative Polymerase Chain Reaction, RNA-seq, Microarray and Immunohistochemistry

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